The present invention concerns the field of needleless syringes used for intradermal, subcutaneous or intramuscular injections of liquid active principle for therapeutic use in human or veterinary medicine.
A needleless syringe is noninvasive by definition: there is no needle passing through the skin in order to bring the active principle to the place where it is to act. For a needleless syringe, it is necessary for the jet of liquid active principle emerging from an orifice or injection conduit to pierce the skin and penetrate to a greater or lesser depth depending on the type of injection desired: to do so, the jet must have a high speed. If the jet is too slow, there is no perforation of the skin, the liquid spreads across the surface of the skin, and it is lost because it produces no therapeutic effect.
In most syringes, the devices for delivering the liquid active principle through the injector are generally displaceable walls of the piston type or of the deformable membrane type which have to be displaced or deformed rapidly, with great acceleration, in order to quickly produce a high-speed jet for piercing the skin.
In patent U.S. Pat. No. 2,322,245, Lockhart describes needleless syringes whose displaceable wall is displaced or driven either by a compressed mechanical spring or by a compressed gas reserve. This drive device acts directly on a rod which impacts a delivery piston situated at a relatively large distance therefrom; the rod is accelerated over this distance by the release of the spring, it impacts the delivery piston, sets it in motion and displaces it quickly enough to atomize the active principle through quite a fine conduit and inject it.
By contrast, for syringes with a pyrotechnic drive, which are described in the same patent, or patents U.S. Pat. No. 3,802,403 and U.S. Pat. No. 4,124,024, the pyrotechnic charge acts directly on the delivery piston or by way of a bellows resting on said piston.
More recently, the patent application WO 95/03844, concerning needleless syringes, again takes up basically the same technique of an impact rod acting on a delivery piston. The impact rod is driven by a mechanical spring or a compressed gas reserve. The drive device is in a high-energy state, and it acts directly on the impact rod which is retained by a lock thereby preventing release of the spring or the compressed gas. During the whole storage period prior to use, the rod and the lock are greatly prestressed.
Opening said lock, directly or by way of a cam, releases the impact rod and the stored energy, which displace the movable components, and injects the liquid. The system changes from a high-energy level to a low-energy level at the end of injection. For disposable syringes, return to the initial state is not possible. Those syringes which are to be used several times comprise auxiliary devices for recompressing the spring and refilling the reservoir of liquid active principle or changing it.
Likewise, patent application WO 97/13537 describes a needleless syringe comprising a displaceable wall and a thrust means consisting of a rod with a piston head. The thrust means is set in motion when the force resulting from the gas pressure of the generator on the piston head is greater than the force resulting from the friction of the piston; the temporary retention thus realized by this equilibrium of the forces translates into quite a slow movement of the displaceable wall.
These devices have several disadvantages. The bioavailability obtained by these devices is not entirely satisfactory. Note that bioavailability is defined by the quantity of liquid actually injected in relation to the quantity initially filling the reservoir of the syringe.
These devices are cumbersome and heavy since they need to be large enough to permit a relatively long course of travel for acceleration of the impact rod. Moreover, spring or compressed gas motors provided for storing a high level of energy for a considerable time prior to use will be structurally quite heavy. Moreover, these devices have problems relating to reliability. In the case of prolonged storage: the spring compressed to the maximum extent degrades; the compressed gas supply will be subject to leaks, and the highly prestressed lock may also experience operating difficulties. In all cases, these devices will be overdimensioned in an attempt to remedy the stated problems of reliability and they will therefore be a little more cumbersome and a little heavier.
The object of the invention is to increase the bioavailability of the active principle by improving the phase of acceleration of the liquid, and also to make available devices which are more compact and reliable.
The present invention concerns a needleless syringe for injection of a liquid active principle initially placed between, on the one hand, an injector comprising at least one injection conduit, said injector being placed in contact with the skin or in immediate proximity to the skin of the subject to be treated, and, on the other hand, a displaceable wall initially separated from a thrust means displaced by the gases from a gas generator and ensuring the pressurization and expulsion of the liquid active principle through the injector placed at the downstream end of the syringe, said syringe being such that said thrust means includes a temporary retention device deactivated by the functioning of the gas generator initiated by a trigger member.
The thrust means is initially separated from the displaceable wall by a short distance which is determined in a manner which we will explain below. The functioning of the gas generator deactivates the temporary retention means, abruptly displaces the thrust means to bring it into contact with the displaceable wall, thereby ensuring very rapid pressurization of the liquid and its injection at high speed. More precisely, the operator acts on a member which triggers the functioning of the gas generator, these latter acting on the thrust means and in doing so deactivating the temporary retention device of said thrust means. By contrast, in the devices of the prior art, the operator acts (directly or indirectly) on a lock, which is a retention device, in order to release the energy necessary for the functioning of the device.
In this invention, liquid active principle will be understood essentially as a more or less viscous liquid, or a mixture of liquids, or a gel. The active principle will be able to be solid in the form of a powder in more or less concentrated suspension in a suitable liquid. The granulometry of the solid and pulverulent active principle must be adapted, as must the shape of the conduit, to avoid blocking of the conduits.
Advantageously for this syringe, the temporary retention device will be breakable: it will be broken upon functioning of the gas generator. Said temporary retention system will be calibrated, that is to say the rupture of the breakable temporary retention device will occur only when the thrust means is subjected, by the effect of the gases from the generator, to a given force, depending in particular on the active principle and on the conditions of use, in order to very quickly obtain a jet of liquid moving at high speed.
Preferably in this syringe the initial distance separating the thrust means from the displaceable wall will be greater than the maximum deformation, before rupture, of the temporary retention device. By observing this condition, the thrust means does not come into contact with the displaceable wall upon deformation of the temporary retention device: there is therefore no liquid delivered at very low speed during the deformation of the breakable temporary retention device.
The initial distance separating the thrust means from the displaceable wall advantageously remains small in order to limit the size of the syringe. Said distance is at most of the order of magnitude of a notable dimension of the thrust means which determines the force acting on the breakable temporary retention device. For example, said distance will remain less than about one tenth of the diameter or of the equivalent diameter of the thrust means.
The gas generator driving the syringe is preferably a pyrotechnic gas generator. This type of gas generator comprises, prior to functioning, a pyrotechnic charge in solid or possibly powder form, a device for initiating the combustion of said charge, and a member for triggering said initiation device. Contrary to the case of a compressed spring, the triggering member is not subjected to any prestressing.
The temporary retention device is advantageously chosen from the group including pins: simple shearable pins or pins with zones of weakening, breakable studs; shearable protective caps which will be sheared in a circle if the thrust means is circular, shearable flanges.
The temporary retention device can also advantageously be an axial rod of which one end is fixed to the thrust means and the other end is fixed to a suitable device on the gas generator side. The rupturing of this axial rod takes place by elongation; this rupture can be controlled by means of a suitably weakened zone of the rod.
To fulfill the function of breakable temporary retention device, it may be possible to use retention devices which are deactivated by deformation or displacement of certain elements; for example, devices with catches which will be deformed or with pawls which will be displaced when said devices are subjected to a substantial and predetermined stress applied to the thrust means.
The thrust means will also advantageously be a piston, in order to limit the size of the device. This piston comprises sealing devices, for example an O-ring seal to ensure correct functioning thereof and to avoid gas leaks toward the active principle reservoir.
In a first embodiment, the displaceable wall will also be a piston, a delivery piston, with sealing devices to form a second level of sealing. By choosing suitable materials for the thrust means and the displaceable wall, it is possible to some extent to control the force of the impact of the two components.
In this embodiment, the pistons constituting the thrust means and the delivery piston have equal or different diameters. However, when the thrust means has a diameter greater than that of the delivery piston, said thrust means has, in its downstream part, a protruding portion whose diameter is at most equal to that of the delivery piston, the length of this protrusion being greater than the course of travel of the thrust means.
In a second embodiment, the displaceable wall will be a deformable membrane. This membrane, preferably thin, will be made of metal or elastomer or plastic material; these materials will be compatible with the active principle. The fixation of said membrane in the syringe will ensure its sealing. This fixation will be achieved, for example, by pinching, crimping or overmolding.
In this embodiment, the downstream face of the thrust means has a shape which is adapted to stamp and deform the deformable membrane on the inner face of the injector so that, at the end of injection, the deformed membrane is sandwiched between the downstream face of the thrust means and the inner face of the injector in order to completely empty the active principle reservoir. We will note that the downstream face of the thrust means and the inner face of the injector have matching shapes.
On account of the power available with a pyrotechnic gas generator and the breakable temporary retention device, a high-speed jet is very quickly obtained for perforating the skin, and the bioavailability of the active principle is thus improved.
The size and the weight of the syringe are reduced by the limitation of the displacement of the thrust means toward the displaceable wall. The compactness of a pyrotechnic gas generator adds further to this effect.
Finally, the reliability of the pyrotechnic gas generators is excellent; in particular, throughout the phase between assembly and use, no element of the pyrotechnic gas generator is subjected to prestressing.
Another advantage of this syringe is linked to the separation of the thrust means and the displaceable wall: it is possible to differentiate between two subassemblies in the syringe. The first one contains the active principle, it is prepared and packaged under the conditions pertaining in the pharmaceutical industry, and the other contains the gas generator, and it too is prepared and packaged under the conditions pertaining to this type of apparatus. The two subassemblies are joined together in a work area in which regulatory and technical constraints are very limited.